title: Discovery of benzothiazole-based adenosine A2B receptor antagonists with improved A2A selectivity.
abstract: The highly potent but modestly selective N-(2-amino-4-methoxy-benzothiazol-7-yl)-N-ethyl-acetamide derivative 2 was selected as the starting point for the design of novel selective A(2B) antagonists, due to its excellent potency, and good drug-like properties. A series of compounds containing nonaromatic amides or ureas of five- or six-membered rings, and also bearing an m-trifluoromethyl-phenyl group (shown to impart superior potency) was prepared and evaluated for their selectivity against the A(2A) and A(1) receptors. This work resulted in the identification of compound 30, with excellent potency and high selectivity against both A(2A) and A(1) receptors.
authors.affiliation: Roche Research Center, Hoffmann-La Roche, Inc, Nutley, NJ 07110, USA.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Firooznia
authors.forename: Adrian Wai-Hing
authors.initials: AW
authors.lastname: Cheung
authors.forename: John
authors.initials: J
authors.lastname: Brinkman
authors.forename: Joseph
authors.initials: J
authors.lastname: Grimsby
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Gubler
authors.forename: Rachid
authors.initials: R
authors.lastname: Hamid
authors.forename: Nicholas
authors.initials: N
authors.lastname: Marcopulos
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Ramsey
authors.forename: Jenny
authors.initials: J
authors.lastname: Tan
authors.forename: Yang
authors.initials: Y
authors.lastname: Wen
authors.forename: Ramakanth
authors.initials: R
authors.lastname: Sarabu
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D013329:Structure-Activity Relationship
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D052160:Benzothiazoles